WO2024090747A1 - Composition comprising cannabidiol and taurine for preventing or treating periodontitis - Google Patents

Composition comprising cannabidiol and taurine for preventing or treating periodontitis Download PDF

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WO2024090747A1
WO2024090747A1 PCT/KR2023/011476 KR2023011476W WO2024090747A1 WO 2024090747 A1 WO2024090747 A1 WO 2024090747A1 KR 2023011476 W KR2023011476 W KR 2023011476W WO 2024090747 A1 WO2024090747 A1 WO 2024090747A1
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taurine
periodontitis
cannabidiol
composition
present
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PCT/KR2023/011476
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French (fr)
Korean (ko)
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소윤조
심현주
임창진
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전북대학교산학협력단
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis

Definitions

  • the present invention relates to a composition for preventing or treating periodontitis containing cannabidiol and taurine.
  • Periodontitis is a chronic inflammatory disease of the periodontitis characterized by destruction of connective tissue and loss of alveolar bone.
  • the main etiological agent of periodontal tissue destruction is dental biofilm containing periodontal pathogenic bacteria, which triggers a host immune response.
  • the Gram-negative anaerobic bacterium Porphyromonas gingivalis one of the major pathogens of periodontitis, releases lipopolysaccharide (LPS) from its outer membrane vesicles.
  • LPS lipopolysaccharide
  • LPS stimulates macrophages to produce tumor necrosis factor- ⁇ (TNF- ⁇ ), interleukin-1 ⁇ (IL-1 ⁇ ), cyclooxygenase (COX), inducible nitric oxide synthase (iNOS), and matrix metalloproteinases.
  • TNF- ⁇ tumor necrosis factor- ⁇
  • IL-1 ⁇ interleukin-1 ⁇
  • COX cyclooxygenase
  • iNOS inducible nitric oxide synthase
  • MMP matrix metalloproteinases
  • CBD Cannabidiol
  • taurine is known to have many physiological functions.
  • taurine is now known to be involved in osmoregulation, membrane stabilization, calcium mobilization, neurotransmission, reproduction, and detoxification.
  • taurine has been reported to provide anti-inflammatory effects and protect cells from the cytotoxic effects of inflammation.
  • the present invention provides a pharmaceutical composition for preventing or treating periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the present invention provides a quasi-drug composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the present invention also provides a food composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the present invention provides a pharmaceutical composition for preventing or treating periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the cannabidiol may be represented by the following formula (1).
  • the taurine may be represented by the following formula (2).
  • the active ingredient can inhibit TNF- ⁇ and IL-1 ⁇ .
  • the present invention provides a quasi-drug composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the present invention provides a food composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the present invention provides a method for preventing or treating periodontitis, comprising administering or taking a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients to an individual.
  • the present invention provides a use for preventing or treating periodontitis of a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • composition according to the present invention can effectively prevent or treat periodontitis by suppressing inflammatory factors and directly suppressing the loss of alveolar bone.
  • it is safe for the human body and has few side effects, so it can be used in a variety of ways as a material for pharmaceuticals, quasi-drugs, or health functional foods.
  • Figure 1 shows the results of intracellular toxicity evaluation of candanibiol and taurine.
  • Figure 2 analyzes the inhibitory efficacy of iNOS and COX-2, inflammatory factors, when treated alone or in combination with candanibiol and taurine.
  • Figure 3 analyzes the efficacy of candanibiol and taurine in suppressing the formation of TRAP-positive cells in macrophages when treated alone or in combination (***, P ⁇ 0.001).
  • Figure 4 analyzes the efficacy of candanibiol and taurine in inhibiting bone loss when treated alone or in combination (***, P ⁇ 0.001).
  • Figure 5 is an analysis of the effect of suppressing pocket depth according to the induction of periodontitis during the combined treatment of candanibiol and taurine (***, P ⁇ 0.001).
  • Figure 6 is an analysis of the effect of suppressing alveolar bone loss caused by periodontitis during combined treatment of candanibiol and taurine (*, P ⁇ 0.05; **, P ⁇ 0.01; ***, P ⁇ 0.001).
  • the present inventors experimentally confirmed that the combined treatment of cannabidiol and taurine had a significantly excellent effect in preventing or treating periodontitis, and completed the present invention.
  • periodontitis treatments developed to date has focused on treating periodontitis by suppressing inflammation.
  • recovery from bone loss caused by inflammation is very difficult or impossible, so prevention by suppressing inflammation is important, but the problem of alveolar bone loss is also important. should be developed in a way that minimizes.
  • the present invention can effectively treat periodontitis by suppressing inflammatory factors and directly suppressing the loss of alveolar bone, and can be usefully used as a material for pharmaceuticals, quasi-drugs, or health functional foods.
  • the present invention provides a composition for preventing or treating (or improving) periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  • the active ingredient has the effect of suppressing inflammatory factors such as TNF- ⁇ and IL-1 ⁇ .
  • the composition may be a pharmaceutical composition, quasi-drug composition, food composition, or health functional food composition.
  • the composition may include cannabidiol:taurine at a concentration ratio of 1:5 to 50.
  • Cannabidiol is a phytocannabinoid discovered in 1940 and is one of 113 cannabinoids identified in Hemp plants. As of 2018, preliminary clinical studies of cannabidiol have included studies of anxiety, cognition, and movement disorders. In the United States, the drug Epidiolex, a cannabidiol drug, has been approved by the U.S. Food and Drug Administration for the treatment of epilepsy.
  • cannabidiol can be represented by the following formula (1).
  • Taurine is a sulfur-containing amine that exists in the cells and tissues of mammals, including humans, and is mainly found in fish and shellfish, especially oysters and scallops, and the dark red flesh of squid, octopus, and fish. Taurine is also known to have a very high level of safety, and one of the characteristics that differentiates it from other amino acids is that even if consumed in excessive amounts, decreased absorption, growth inhibition, or other side effects have not been reported.
  • taurine can be represented by the following formula (2).
  • the method for obtaining cannabidiol and taurine of the present invention is not particularly limited, and can be isolated from natural products, chemically synthesized using a known production method, or commercially available cannabidiol can be used.
  • cannabidiol and taurine may include hydrates, derivatives, etc. within the range of having the same efficacy, and may include solvates or stereoisomers thereof.
  • prevention refers to any action that delays the onset of periodontitis by administration of the composition of the present invention
  • treatment and “improvement” refers to the improvement or beneficial change in symptoms of periodontitis by administration of the composition of the present invention. It means all actions.
  • the term “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid.
  • Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction.
  • the free acid may be an inorganic acid or an organic acid.
  • Non-limiting examples of the inorganic acid include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc., and these may be used alone or in a mixture of two or more types.
  • the “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid.
  • Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction.
  • an acid or alcohol e.g., glycol monomethyl ether
  • the salts of cannabidiol and taurine may include all salts of acidic or basic groups that may be present in the compounds of cannabidiol and taurine.
  • the salts of cannabidiol and taurine may include sodium, calcium, and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hadrobromide, sulfuric acid, hydrogen sulfate, and phosphate. , hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, etc., which are known in the art. It can be produced through a known salt production method.
  • composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients
  • compositions of the present invention can be prepared as pharmaceutical compositions.
  • the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.
  • the composition of the present invention includes (a) a pharmaceutically effective amount of cannabidiol and taurine of the present invention described above; and (b) a pharmaceutically acceptable carrier.
  • pharmaceutically effective amount refers to an amount sufficient to achieve the efficacy or activity of cannabidiol and taurine described above.
  • Pharmaceutically acceptable carriers are commonly used, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrroli. Includes, but is not limited to, money, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
  • composition of the present invention can be administered orally or parenterally.
  • the appropriate dosage of the pharmaceutical composition of the present invention is prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be.
  • the general dosage of the pharmaceutical composition of the present invention is within the range of 0.001-100 mg/kg for adults. Administration may be administered once a day, or may be administered in several divided doses. However, the scope of the present invention is not limited by the above dosage.
  • the pharmaceutical composition of the present invention is prepared in unit dosage form by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by those skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be in the form of a solution, suspension, syrup or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally contain a dispersant or stabilizer.
  • Quasi-drug composition containing cannabidiol and taurine, or pharmaceutically acceptable salts thereof, as active ingredients
  • composition of the present invention may be provided as a quasi-drug composition.
  • the above active ingredients may be added as is, or other components commonly used in oral quasi-drug compositions may be included, such as abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, flavoring agents, colorants, solvents, and whitening agents. , solubilizers, or pH adjusters.
  • the mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).
  • Quasi-drug compositions can be manufactured in any formulation commonly manufactured in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish, oral rinse, and gum. It may have a formulation such as massage cream, but is not limited thereto.
  • the quasi-drug composition of the present invention when in the form of a toothpaste, it may include a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetener, a coloring agent, a preservative, a medicinal ingredient, a solvent, a pH adjuster, etc.
  • the composition of the present invention may be provided as a food composition or health functional food composition.
  • the composition of the present invention includes not only the cannabidiol and taurine as active ingredients, but also ingredients commonly added during food production, such as proteins, carbohydrates, fats, nutrients, and seasoning. Includes agents and flavoring agents.
  • the above-mentioned carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents [thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
  • synthetic flavoring agents sacharin, aspartame, etc.
  • citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, Eucommia extract, jujube extract, licorice extract, etc. may be additionally included. there is.
  • the formulation of the food composition or health functional food composition can be in the form of powders, granules, pills, tablets, capsules, as well as general foods or beverages.
  • the active ingredient when manufacturing food or beverages, can be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of raw materials.
  • the amount in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since the present invention uses natural substances, there is no safety problem, so the amount above the above range. It can also be used.
  • Cannabidiol was synthesized using olivetol and camphor according to a previously known synthesis method. (V. Vaillancourt and K.F. Albizati., 1992). Taurine was purchased and used from (Sigma-Aldrich, Korea).
  • CBD and taurine intracellular toxicity evaluation was performed on osteoclasts (Raw264.7 cells), which are inflammatory cells, and the results are shown in Figure 1.
  • CBD was found to have no intracellular toxicity up to 12 uM
  • taurine was found to have no intracellular toxicity up to a concentration of 0.6 mM.
  • the appropriate concentrations for each were determined to be CBD (10 uM) and Taurine (0.5 mM), and subsequent intracellular toxicity evaluation according to the combined treatment was conducted. As a result, it was confirmed that the combination of CBD and taurine had no intracellular toxicity.
  • TRAP formation and the degree of bone loss by RANKL were analyzed through pit formation area analysis.
  • Rats were purchased from Nara Biotech Pyeongtaek Plant (Gyeonggi-do, Korea), and the rats used in the test were 6-week-old Sprague-Dawley male rats (M/6W, 180-200g). Animal experiments were conducted in accordance with the regulations of the Chonbuk National University Institutional Animal Care and Use Committee (IACUC guidelines).
  • the rats tested were exposed to the experimental environment by consuming free food and drinking water for one week in an animal breeding room maintained at 20-24°C and humidity at 50-60%, with the day and night cycles adjusted to 12 hours each. adapted.
  • Periodontitis bacteria (P. gingivalis) was purchased from the Korea Oral Microbial Resources Bank (PG 2797). Periodontitis-causing bacteria were prepared by inoculating the culture medium in an anaerobic bench 3 weeks before the start of the experiment and culturing for 3 weeks. Periodontitis bacteria cultured for 3 weeks were used to induce periodontitis for 7 days, using the turbidity of the culture medium visually and the growth rate of the bacteria inoculated in the culture dish.
  • Periodontitis is induced by ligature using a band treated with periodontitis bacteria (TP Orthodontics, Inc., Seoul, Korea).
  • the band suture was stored in a slurry containing periodontitis bacteria so that the band suture could be processed while the periodontitis bacteria were well mixed into the band.
  • the bonding band was excised to an appropriate size and then ligatured to the area in front of the maxillary molars (premolar of mandibular quadrant) to induce periodontitis. After 3 days, loss of the bonding band was confirmed, and the bonding band was inserted again into the lost area to treat periodontitis for 7 days. caused.
  • the total number of animals presented in the experiment was 50, and a total of 50 animals in 5 treatments, 10 animals in each treatment group, were used in the experiment. Among the 50 animals, 10 animals were used in each treatment group. Control is a healthy group in which periodontitis was not induced, and vehicle is a control group in which only water was administered without medication after periodontitis was induced. In addition, Insadol (4.5 mg/kg Dongkook Pharmaceutical, Korea) was purchased commercially as a control and was administered by dissolving it in water.
  • Low dose CBD + Taurine (L-CBD + Taurine) and high dose CBD + Taurine (H-CBD + Taurine) treatments were treated with Taurine (100mg/kg Sigma-Aldrich, Seoul, Korea) to examine the efficacy of periodontitis according to CBD concentration. ) was dissolved in water and administered at a fixed concentration, and CBD was not soluble in water, so it was dissolved in corn oil (Sigma-Aldrich) and administered at a concentration of L-CBD (2 mg/kg) and H-CBD (20mg/kg). .
  • Pocket depth was measured using a pocket depth probe.
  • the effect of suppressing periodontitis upon administration of the preparation after inducing periodontitis was measured using the length of pocket depth.
  • the measurement period was measured three times on the 7th, 14th, and 21st days after the induction of periodontitis to examine the efficacy of suppressing periodontitis.
  • Aleveolar bone loss was measured using high resolution in vivo After inducing total periodontitis, the preparation was administered until the 20th day, and then Sacrificed on the 21st day, the right maxillary bone was sampled and micro-CT was measured. Bone mineral density (BMD) of each treatment group was measured using two-dimensional measurement software (Bruker dataviewer, USA).
  • the pharmaceutical or food composition of Preparation Example 1 or 2 was prepared according to a conventional method according to the composition ingredients and composition ratios as follows.
  • tablets were manufactured by tableting according to a conventional tablet manufacturing method.
  • a capsule was prepared by filling a gelatin capsule according to a typical capsule preparation method.
  • the above ingredients are dissolved in purified water according to the usual manufacturing method, an appropriate amount of lemon flavor is added, then purified water is added to adjust the total to 100 mL, then sterilized and filled into a brown bottle to prepare a liquid.
  • Vitamin A acetate 70 ⁇ g
  • Vitamin B 1 0.13 mg
  • Vitamin B 2 0.15 mg
  • Vitamin B 6 0.5 mg
  • Vitamin B 12 0.2 ⁇ g
  • composition ratio of the above vitamin and mineral mixture is a mixture of components relatively suitable for health food in a preferred embodiment, but the mixing ratio may be modified arbitrarily.
  • the above ingredients are mixed according to a typical health food manufacturing method, and then , granules can be manufactured and used to manufacture health food compositions according to conventional methods.
  • Vitamin A 0.2 g
  • Vitamin B1 0.25 g
  • Vitamin B2 0.3 g
  • composition ratio is a preferred embodiment of mixing ingredients that are relatively suitable for beverages of preference, but the mixing ratio may be arbitrarily modified depending on regional or ethnic preferences such as demand class, country of demand, and intended use.

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Abstract

The present invention relates to a composition comprising cannabidiol and taurine for preventing or treating periodontitis. The composition according to the present invention can inhibit inflammatory factors and directly inhibit alveolar bone loss, and thus can effectively prevent or treat periodontitis. In addition, the present invention is safe for the human body and has few side effects, and thus can be variously used in materials for medicines, quasi-drugs, health functional foods and the like.

Description

칸나비디올 및 타우린을 포함하는 치주염 예방 또는 치료용 조성물 Composition for preventing or treating periodontitis comprising cannabidiol and taurine
본 출원은 2022년 10월 24일 출원된 대한민국 특허출원 제10-2022-0137558호를 우선권으로 주장하고, 상기 명세서 전체는 본 출원의 참고문헌이다. This application claims priority to Republic of Korea Patent Application No. 10-2022-0137558, filed on October 24, 2022, and the entire specification is a reference to this application.
본 발명은 칸나비디올 및 타우린을 포함하는 치주염 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating periodontitis containing cannabidiol and taurine.
치주염은 결합조직의 파괴와 치조골의 소실을 특징으로 하는 치주염의 만성 염증성 질환이다. 치주 조직 파괴의 주요 병인은 치주병성 박테리아를 포함하는 치과 생물막(Bio film)으로 숙주 면역 반응을 유발한다. 예를 들어, 그람 음성 혐기성 세균 Porphyromonas gingivalis는 치주염의 주요 병원체 중 하나로서 외막 소포에서 지질다당류(LPS)를 방출한다. LPS는 대식세포를 자극하여 종양 괴사 인자-α(TNF-α), 인터루킨-1β(IL-1β), 시클로옥시게나제(COX), 유도성 산화질소 신타제(iNOS) 및 기질 금속단백분해효소(MMP)를 포함한 전염증 매개체를 분비한다. 이러한 분자는 대부분 치주염에서 치조골 흡수의 잠재적 매개체로 작용한다.Periodontitis is a chronic inflammatory disease of the periodontitis characterized by destruction of connective tissue and loss of alveolar bone. The main etiological agent of periodontal tissue destruction is dental biofilm containing periodontal pathogenic bacteria, which triggers a host immune response. For example, the Gram-negative anaerobic bacterium Porphyromonas gingivalis, one of the major pathogens of periodontitis, releases lipopolysaccharide (LPS) from its outer membrane vesicles. LPS stimulates macrophages to produce tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase (COX), inducible nitric oxide synthase (iNOS), and matrix metalloproteinases. Secretes pro-inflammatory mediators, including (MMP). Most of these molecules act as potential mediators of alveolar bone resorption in periodontitis.
치주 연구에서는 동물을 이용한 결찰 유발 치주염이 개발되었다. 예를 들어, 설치류 모델은 치주 질환 메커니즘을 조사하는 데 널리 사용되었다. 결찰은 치은하 영역에서 박테리아의 국소 축적을 유도하고 박테리아 매개 염증 및 골 손실을 향상시킨다. In periodontal research, ligation-induced periodontitis using animals has been developed. For example, rodent models have been widely used to investigate periodontal disease mechanisms. Ligation induces local accumulation of bacteria in the subgingival region and enhances bacterial-mediated inflammation and bone loss.
칸나비디올(Cannabidiol, CBD)은 대마(Cannabis)에서 분리 추출된 물질로 THC와 함께 대마의 주요 생리활성 물질로, 다양한 질환에 효과가 있다고 보고되었다. 특히 CBD 관련 수용체(receptor)가 뼈의 형성에 중요하게 작용한다고 보고되어 있어 뼈의 소실억제 및 뼈의 형성에 CBD가 간접적으로 작용한다고 알려져 있다. 또한 CBD는 rheumatoid arthritis synovial fibroblasts의 염증억제에 중요하게 작용하여 치주염에서 염증과 관련된 중요한 사이토카인(IL-1b, TNF-a, iNOS, Cox-2 등)을 억제한다. 하지만 직접적인 치과 질환에 의한 염증성 억제와 동시에 치주골 소실을 억제한다는 보고는 거의 없는 실정이다.Cannabidiol (CBD) is a substance isolated and extracted from cannabis. It is the main bioactive substance of cannabis along with THC, and has been reported to be effective in various diseases. In particular, CBD-related receptors have been reported to play an important role in bone formation, and it is known that CBD indirectly acts to inhibit bone loss and bone formation. In addition, CBD plays an important role in suppressing inflammation in rheumatoid arthritis synovial fibroblasts, suppressing important cytokines (IL-1b, TNF-a, iNOS, Cox-2, etc.) related to inflammation in periodontitis. However, there are few reports that it directly suppresses inflammation caused by dental disease and simultaneously suppresses periodontal bone loss.
한편 타우린 (Taurine)은 많은 생리적 기능을 가지고 있는 것으로 알려져 있다. 예를 들어, 타우린은 현재 삼투압 조절, 막 안정화, 칼슘 동원, 신경 전달, 생식 및 해독에 관여하는 것으로 알려져 있다. 특히, 타우린은 항염증 효과를 제공하고 염증의 세포독성 효과로부터 세포를 보호하는 것으로 보고된 바 있다. 하지만 치주염 치료 효과에 대한 보고는 거의 없는 실정이다.Meanwhile, taurine is known to have many physiological functions. For example, taurine is now known to be involved in osmoregulation, membrane stabilization, calcium mobilization, neurotransmission, reproduction, and detoxification. In particular, taurine has been reported to provide anti-inflammatory effects and protect cells from the cytotoxic effects of inflammation. However, there are almost no reports on the effectiveness of treating periodontitis.
본 발명은 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
또한 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
또한 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 식품 조성물을 제공한다.The present invention also provides a food composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
그러나, 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.
본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
상기 칸나비디올은 하기 화학식 1로 표시될 수 있다.The cannabidiol may be represented by the following formula (1).
[화학식 1][Formula 1]
Figure PCTKR2023011476-appb-img-000001
Figure PCTKR2023011476-appb-img-000001
상기 타우린은 하기 화학식 2로 표시될 수 있다.The taurine may be represented by the following formula (2).
[화학식 2][Formula 2]
Figure PCTKR2023011476-appb-img-000002
Figure PCTKR2023011476-appb-img-000002
상기 유효성분은 TNF-α 및 IL-1β를 억제할 수 있다.The active ingredient can inhibit TNF-α and IL-1β.
또한, 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
또한, 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving periodontitis containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
또한, 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 조성물을 개체에 투여 또는 복용시키는 단계를 포함하는 치주염 예방 또는 치료방법을 제공한다.In addition, the present invention provides a method for preventing or treating periodontitis, comprising administering or taking a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients to an individual.
또한, 본 발명은, 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 조성물의 치주염 예방 또는 치료용도를 제공한다.In addition, the present invention provides a use for preventing or treating periodontitis of a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
본 발명에 따른 조성물은, 염증 인자를 억제하고 치조골의 소실을 직접적으로 억제함으로써 치주염을 효과적으로 예방 또는 치료할 수 있다. 또한, 인체에 안전하며 부작용이 거의 없어 의약품, 의약외품 또는 건강기능식품 등의 소재로 다양하게 활용될 수 있다The composition according to the present invention can effectively prevent or treat periodontitis by suppressing inflammatory factors and directly suppressing the loss of alveolar bone. In addition, it is safe for the human body and has few side effects, so it can be used in a variety of ways as a material for pharmaceuticals, quasi-drugs, or health functional foods.
도 1은 칸다니비올 및 타우린의 세포내 독성 평가 결과를 나타내는 것이다.Figure 1 shows the results of intracellular toxicity evaluation of candanibiol and taurine.
도 2는 칸다니비올 및 타우린의 단독, 병용 처리시의 염증인자인 iNOS, COX-2의 억제 효능을 분석한 것이다.Figure 2 analyzes the inhibitory efficacy of iNOS and COX-2, inflammatory factors, when treated alone or in combination with candanibiol and taurine.
도 3은 칸다니비올 및 타우린의 단독, 병용 처리시의 대식세포에서의 TRAP 양성 세포의 형성 억제 효능을 분석한 것이다(***, P〈0.001).Figure 3 analyzes the efficacy of candanibiol and taurine in suppressing the formation of TRAP-positive cells in macrophages when treated alone or in combination (***, P < 0.001).
도 4는 칸다니비올 및 타우린의 단독, 병용 처리시의 골 소실 억제 효능을 분석한 것이다 (***, P〈0.001). Figure 4 analyzes the efficacy of candanibiol and taurine in inhibiting bone loss when treated alone or in combination (***, P<0.001).
도 5는 칸다니비올 및 타우린의 병용 처리시의 치주염 유발에 따른 Pocket depth 억제 효과를 분석한 것이다 (***, P〈0.001).Figure 5 is an analysis of the effect of suppressing pocket depth according to the induction of periodontitis during the combined treatment of candanibiol and taurine (***, P < 0.001).
도 6은 칸다니비올 및 타우린의 병용 처리시의 치주염 유발에 따른 치조골 소실(Alveolar bone loss) 억제 효과를 분석한 것이다 (*, P〈0.05; **, P〈0.01; ***, P〈0.001). Figure 6 is an analysis of the effect of suppressing alveolar bone loss caused by periodontitis during combined treatment of candanibiol and taurine (*, P < 0.05; **, P < 0.01; ***, P < 0.001).
본 발명자들은 칸나비디올과 타우린의 병용 처리시, 치주염 예방 또는 치료 효과가 현저히 우수하다는 것을 실험적으로 확인하고, 본 발명을 완성하였다.The present inventors experimentally confirmed that the combined treatment of cannabidiol and taurine had a significantly excellent effect in preventing or treating periodontitis, and completed the present invention.
현재까지 개발된 치주염 치료제의 개발은 염증성 억제를 통한 치주염 치료에 초점이 맞춰져 있지만 치주염은 염증에 의해 발생되는 골 소실의 회복이 매우 어렵거나 불가능하므로 염증 억제를 통한 예방도 중요하지만 치조골이 소실되는 문제를 최소화하는 방향으로 개발되어야 한다. The development of periodontitis treatments developed to date has focused on treating periodontitis by suppressing inflammation. However, in periodontitis, recovery from bone loss caused by inflammation is very difficult or impossible, so prevention by suppressing inflammation is important, but the problem of alveolar bone loss is also important. should be developed in a way that minimizes.
본 발명은, 염증 인자를 억제하고 치조골의 소실을 직접적으로 억제함으로써 치주염을 효과적으로 치료할 수 있어, 의약품, 의약외품 또는 건강기능식품 등의 소재로 유용하게 활용될 수 있다. The present invention can effectively treat periodontitis by suppressing inflammatory factors and directly suppressing the loss of alveolar bone, and can be usefully used as a material for pharmaceuticals, quasi-drugs, or health functional foods.
이하, 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 치료용(또는 개선용) 조성물을 제공한다.The present invention provides a composition for preventing or treating (or improving) periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
상기 유효성분은 TNF-α 및 IL-1β 등과 같은 염증 인자를 억제 효능을 갖는다.The active ingredient has the effect of suppressing inflammatory factors such as TNF-α and IL-1β.
상기 조성물은 약학적 조성물, 의약외품 조성물, 식품 조성물 또는 건강기능식품 조성물일 수 있다.The composition may be a pharmaceutical composition, quasi-drug composition, food composition, or health functional food composition.
상기 조성물은 칸나비디올 : 타우린을 1 : 5 ~ 50의 농도비로 포함할 수 있다. The composition may include cannabidiol:taurine at a concentration ratio of 1:5 to 50.
칸나비디올(cannabidiol, CBD)은 1940년에 발견된 식물칸나비노이드로, 삼속 식물에서 식별된 113개의 카나비노이드 가운데 하나이다. 2018년 기준으로, 칸나비디올의 예비 임상 연구에는 불안, 인식, 운동장애 등의 연구가 포함된 바 있다. 미국에서 칸나비디올의 약제인 에피디올렉스라는 약물은 뇌전증 질환 치료를 위해 미국 식품의약국에 의해 승인된 바 있다.Cannabidiol (CBD) is a phytocannabinoid discovered in 1940 and is one of 113 cannabinoids identified in Hemp plants. As of 2018, preliminary clinical studies of cannabidiol have included studies of anxiety, cognition, and movement disorders. In the United States, the drug Epidiolex, a cannabidiol drug, has been approved by the U.S. Food and Drug Administration for the treatment of epilepsy.
상기 칸나비디올의 구조는 하기 화학식 1로 표시될 수 있다.The structure of cannabidiol can be represented by the following formula (1).
[화학식 1][Formula 1]
Figure PCTKR2023011476-appb-img-000003
Figure PCTKR2023011476-appb-img-000003
타우린은 인간을 비롯한 포유동물의 세포와 조직에 존재하는 유황을 함유하는 아민으로서, 주로 어패류 특히 굴, 가리비 등 조개류나 오징어, 문어, 생선의 검붉은 살 등에 많이 함유되어 있다. 타우린은 또한 안전성이 매우 높은 것으로 알려져 있는데, 다른 아미노산과 차별화되는 특징 중 하나는 과량을 섭취하여도 흡수율 감소나 성장 저해 및 그 외 다른 부작용이 보고된 바 없다.Taurine is a sulfur-containing amine that exists in the cells and tissues of mammals, including humans, and is mainly found in fish and shellfish, especially oysters and scallops, and the dark red flesh of squid, octopus, and fish. Taurine is also known to have a very high level of safety, and one of the characteristics that differentiates it from other amino acids is that even if consumed in excessive amounts, decreased absorption, growth inhibition, or other side effects have not been reported.
상기 타우린의 구조는 하기 화학식 2로 표시될 수 있다.The structure of taurine can be represented by the following formula (2).
[화학식 2][Formula 2]
Figure PCTKR2023011476-appb-img-000004
Figure PCTKR2023011476-appb-img-000004
본 발명의 칸나비디올, 타우린의 수득 방법은 수득 방법은 특별히 한정되지 않으며, 천연물에서 분리하거나, 공지된 제법을 사용하여 화학적으로 합성하거나, 시판되는 것을 사용할 수 있다.The method for obtaining cannabidiol and taurine of the present invention is not particularly limited, and can be isolated from natural products, chemically synthesized using a known production method, or commercially available cannabidiol can be used.
본 발명에서, 칸나비디올, 타우린은 이와 동일한 효능을 갖는 범위 내에서 수화물, 유도체 등을 포함할 수 있으며, 이의 용매화합물이나 입체 이성질체를 포함할 수 있다.In the present invention, cannabidiol and taurine may include hydrates, derivatives, etc. within the range of having the same efficacy, and may include solvates or stereoisomers thereof.
본 명세서 내 "예방"은 본 발명의 조성물의 투여로 치주염의 발병을 지연시키는 모든 행위를 의미하고, "치료" 및 "개선"은 본 발명의 조성물의 투여로 치주염의 증세가 호전 또는 이롭게 변경되는 모든 행위를 의미한다.As used herein, “prevention” refers to any action that delays the onset of periodontitis by administration of the composition of the present invention, and “treatment” and “improvement” refers to the improvement or beneficial change in symptoms of periodontitis by administration of the composition of the present invention. It means all actions.
본 발명에서, 용어 "약학적으로 허용 가능한 염" 또는 "이의 염"은 유리산(free acid)에 의해 형성된 산 부가염일 수 있다. 산 부가염은 통상의 방법, 예를 들어 화합물을 과량의 산 수용액에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들어 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조할 수 있다. 또한, 동 몰량의 화합물 및 물 중의 산 또는 알코올 (예를 들어, 글리콜 모노메틸 에테르)을 가열하고, 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다. 상기 유리산으로는 무기산 또는 유기산을 사용할 수 있다 상기 무기산의 비제한적인 예로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있으며, 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다. 상기 "약학적으로 허용 가능한 염" 또는 "이의 염"은 유리산(free acid)에 의해 형성된 산 부가염일 수 있다. 산 부가염은 통상의 방법, 예를 들어 화합물을 과량의 산 수용액에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들어 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조할 수 있다. 또한, 동 몰량의 화합물 및 물 중의 산 또는 알코올 (예를 들어, 글리콜 모노메틸 에테르)을 가열하고, 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다.In the present invention, the term “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction. The free acid may be an inorganic acid or an organic acid. Non-limiting examples of the inorganic acid include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc., and these may be used alone or in a mixture of two or more types. The “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Additionally, equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction.
상기 칸나비디올, 타우린의 염은, 달리 지시되지 않는 한, 상기 칸나비디올, 타우린의 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 모두 포함할 수 있다. 예를 들어 상기 칸나비디올, 타우린의 염으로는 하이드록시기의 나트륨, 칼슘 및 칼륨염 등이 포함될 수 있고, 아미노기의 기타 약학적으로 허용 가능한 염으로는 하드로브로마이드, 황산, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄술포네이트 (메실레이트) 및 p-톨루엔술포네이트 (토실레이트)염 등을 들 수 있으며 당업계에서 알려진 염의 제조방법을 통하여 제조될 수 있다.Unless otherwise indicated, the salts of cannabidiol and taurine may include all salts of acidic or basic groups that may be present in the compounds of cannabidiol and taurine. For example, the salts of cannabidiol and taurine may include sodium, calcium, and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hadrobromide, sulfuric acid, hydrogen sulfate, and phosphate. , hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, etc., which are known in the art. It can be produced through a known salt production method.
칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 약학적 조성물Pharmaceutical composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients
본 발명의 조성물은 약학적 조성물로 제조될 수 있다.The compositions of the present invention can be prepared as pharmaceutical compositions.
본 발명의 조성물이 약학적 조성물로 제조되는 경우, 본 발명의 약학적 조성물은 약학적으로 허용되는 담체를 포함할 수 있다.When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.
본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물은 (a) 상술한 본 발명의 칸나비디올 및 타우린의 약학적 유효량; 및 (b) 약학적으로 허용되는 담체를 포함하는 약학적 조성물일 수 있다. 본 명세서에서 용어 "약학적 유효량"은 상술한 칸나비디올 및 타우린의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다.According to a preferred embodiment of the present invention, the composition of the present invention includes (a) a pharmaceutically effective amount of cannabidiol and taurine of the present invention described above; and (b) a pharmaceutically acceptable carrier. As used herein, the term “pharmaceutically effective amount” refers to an amount sufficient to achieve the efficacy or activity of cannabidiol and taurine described above.
약학적으로 허용되는 담체는 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.Pharmaceutically acceptable carriers are commonly used, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrroli. Includes, but is not limited to, money, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약학적 조성물은 경구 또는 비경구 투여할 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally.
본 발명의 약학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 약학적 조성물의 일반적인 투여량은 성인 기준으로 0.001-100 ㎎/kg 범위 내이다. 투여는 하루에 한 번 투여할 수도 있고, 수회 나누어서 투여할 수도 있다. 다만, 상기 투여량에 의해서 본 발명의 범위를 한정하는 것은 아니다.The appropriate dosage of the pharmaceutical composition of the present invention is prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be. The general dosage of the pharmaceutical composition of the present invention is within the range of 0.001-100 mg/kg for adults. Administration may be administered once a day, or may be administered in several divided doses. However, the scope of the present invention is not limited by the above dosage.
본 발명의 약학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by those skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be in the form of a solution, suspension, syrup or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally contain a dispersant or stabilizer.
칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 의약외품 조성물Quasi-drug composition containing cannabidiol and taurine, or pharmaceutically acceptable salts thereof, as active ingredients
본 발명의 조성물은 의약외품 조성물로 제공될 수 있다.The composition of the present invention may be provided as a quasi-drug composition.
상기 유효성분을 그대로 첨가하거나, 이외에 구강용 의약외품 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예컨대 연마제, 습윤제, 결합제, 기포제, 감미제, 방부제, 약효성분, 향미제, 색소, 용제, 증백제, 가용화제 또는 pH 조정제 등을 포함할 수 있다. 유효성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. The above active ingredients may be added as is, or other components commonly used in oral quasi-drug compositions may be included, such as abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, flavoring agents, colorants, solvents, and whitening agents. , solubilizers, or pH adjusters. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).
의약외품 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 치약, 구강세정제, 구강청정제, 껌, 캔디류, 구강스프레이, 구강용 연고제, 구강용 바니쉬, 구강양치액 및 잇몸 마사지 크림 등의 제형을 가질 수 있으나 이에 제한되는 것은 아니다.Quasi-drug compositions can be manufactured in any formulation commonly manufactured in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish, oral rinse, and gum. It may have a formulation such as massage cream, but is not limited thereto.
하나의 예로서, 본 발명의 의약외품 조성물이 치약의 제형일 경우, 습윤제, 연마제, 결합제, 기포제, 향미제, 감미제, 착색제, 보존제, 약효성분, 용제, pH 조절제 등을 포함할 수 있다.As an example, when the quasi-drug composition of the present invention is in the form of a toothpaste, it may include a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetener, a coloring agent, a preservative, a medicinal ingredient, a solvent, a pH adjuster, etc.
칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 식품 조성물A food composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
본 발명의 조성물은 식품 조성물 또는 건강기능식품 조성물로 제공될 수 있다. 본 발명의 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 상기 칸나비디올, 타우린 뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)] 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 천연물 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.The composition of the present invention may be provided as a food composition or health functional food composition. When the composition of the present invention is manufactured as a food composition, it includes not only the cannabidiol and taurine as active ingredients, but also ingredients commonly added during food production, such as proteins, carbohydrates, fats, nutrients, and seasoning. Includes agents and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent, natural flavoring agents [thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is manufactured as a drink, in addition to the natural product extract of the present invention, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, Eucommia extract, jujube extract, licorice extract, etc. may be additionally included. there is.
상기 식품 조성물 또는 건강기능식품 조성물의 제형은 산제, 과립제, 환, 정제, 캡슐제의 형태뿐만 아니라 일반 식품 또는 음료의 형태 어느 것이나 가능하다.The formulation of the food composition or health functional food composition can be in the form of powders, granules, pills, tablets, capsules, as well as general foods or beverages.
상기 식품의 종류에는 특별히 제한은 없고, 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸콜렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함할 수 있다.There are no particular restrictions on the type of food, and examples of foods to which the above substance can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, and dairy products including ice cream. , various soups, beverages, teas, drinks, alcoholic beverages, and vitamin complexes, etc., and can include all foods in the conventional sense.
일반적으로, 식품 또는 음료의 제조시에 상기 유효성분은 원료 100 중량부에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가할 수 있다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 또한 본 발명은 천연물질을 이용하는 점에서 안전성 면에서 문제가 없으므로 상기 범위 이상의 양으로도 사용할 수 있다.In general, when manufacturing food or beverages, the active ingredient can be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since the present invention uses natural substances, there is no safety problem, so the amount above the above range. It can also be used.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.
실시예 Example
칸나비디올(Cannabidiol, CBD)은 olivetol과 camphor를 이용하여 기존에 알려진 합성법에 따라 합성한 후 사용하였다. (V. Vaillancourt 와 K. F. Albizati., 1992). 타우린(Taurine)은 (Sigma-Aldrich, korea)사에서 구매하여 사용하였다. Cannabidiol (CBD) was synthesized using olivetol and camphor according to a previously known synthesis method. (V. Vaillancourt and K.F. Albizati., 1992). Taurine was purchased and used from (Sigma-Aldrich, Korea).
실시예 1. 세포독성 평가Example 1. Cytotoxicity evaluation
CBD와 타우린에 대하여, 염증성 세포인 파골세포 (Raw264.7 cell)에서 세포내 독성평가를 실시하고 그 결과를 도 1에 나타내었다. CBD의 경우 12 uM까지 세포내 독성이 없는 것으로 나타났고, 타우린의 경우 0.6 mM의 농도까지 세포내 독성이 없는 것으로 확인되었다. 각각의 적정 농도를 CBD (10 uM)와 Taurine (0.5 mM)로 판단하여 이후 병용처리에 따른 세포내 독성 평가를 실시하였다. 그 결과 CBD 및 타우린의 조합에서 모두 세포내 독성이 없는 것으로 확인되었다.For CBD and taurine, intracellular toxicity evaluation was performed on osteoclasts (Raw264.7 cells), which are inflammatory cells, and the results are shown in Figure 1. CBD was found to have no intracellular toxicity up to 12 uM, and taurine was found to have no intracellular toxicity up to a concentration of 0.6 mM. The appropriate concentrations for each were determined to be CBD (10 uM) and Taurine (0.5 mM), and subsequent intracellular toxicity evaluation according to the combined treatment was conducted. As a result, it was confirmed that the combination of CBD and taurine had no intracellular toxicity.
실시예 2. 염증관련 인자 억제 효능 분석Example 2. Analysis of efficacy of inhibiting inflammation-related factors
CBD와 타우린의 염증 관련 인자인 COX-2, iNOS에 대한 억제 효과를 실험하였다. 대식세포인 RAW264.7 cell에 염증 유도 물질인 LPS를 처리하여 CBD와 타우린 단독 염증 억제 효과 및 병용 처리에 따른 염증 효과를 분석하였다. 분석 결과, CBD 및 타우린을 병용하여 사용하는 경우 iNOS의 억제 효능 및 COX-2 억제 효능이 현저히 상승하는 것으로 확인되었다(도 2).The inhibitory effects of CBD and taurine on inflammation-related factors COX-2 and iNOS were tested. RAW264.7 cells, which are macrophages, were treated with LPS, an inflammation-inducing substance, and the anti-inflammatory effect of CBD and taurine alone and the inflammatory effect of combined treatment were analyzed. As a result of the analysis, it was confirmed that when CBD and taurine were used in combination, the inhibitory efficacy of iNOS and COX-2 were significantly increased (Figure 2).
실시예 3. 골 소실 억제 효능 분석Example 3. Bone loss inhibition efficacy analysis
CBD 및 타우린의 치주염에 의한 골 소실 억제 효능을 확인하기 위하여, pit formation area 분석을 통하여 RANKL에 의한 TRAP 형성과 골 소실 정도를 분석하였다.In order to confirm the effectiveness of CBD and taurine in suppressing bone loss caused by periodontitis, TRAP formation and the degree of bone loss by RANKL were analyzed through pit formation area analysis.
파골세포의 분화 시 RANKL에 의한 TRAP 양성 세포 형성 억제 정도를 분석한 결과, CBD 또는 타우린 단독 처리시 TRAP 양성 세포 형성 억제 효능이 매우 낮았으나, CBD 및 타우린을 병용하여 사용하는 경우 RAP 양성 세포 형성 억제 효능이 매우 높은 것으로 확인되었다(도 3). As a result of analyzing the degree of inhibition of TRAP-positive cell formation by RANKL during osteoclast differentiation, the efficacy of inhibiting TRAP-positive cell formation was very low when CBD or taurine was used alone, but when CBD and taurine were used in combination, RAP-positive cell formation was inhibited. It was confirmed that the efficacy was very high (Figure 3).
또한, CBD 및 타우린의 골 소실 억제 효능을 확인하기 위하여, 대식세포에서 RANKL에 의한 골 소실 억제 정도를 분석하였다. CBD, 타우린 각각을 단독 처리한 경우 골 소실 억제 효능이 거의 없거나 매우 낮았으나, CBD 및 타우린을 병용하여 사용하는 경우 골 소실 억제 효능이 매우 높은 것으로 확인되었다(도 4). In addition, in order to confirm the efficacy of CBD and taurine in suppressing bone loss, the degree of inhibition of bone loss by RANKL in macrophages was analyzed. When CBD and taurine were treated alone, the bone loss inhibition efficacy was almost or very low, but when CBD and taurine were used in combination, the bone loss inhibition efficacy was confirmed to be very high (Figure 4).
따라서, CBD와 타우린을 병용 처리하는 경우, 염증인자 및 염증성 치주염 억제 효과가 매우 우수하며, 염증에 의해 발생되는 치조골의 소실 억제 효과도 매우 우수하다는 것을 알 수 있다.Therefore, it can be seen that when CBD and taurine are combined, the effect of suppressing inflammatory factors and inflammatory periodontitis is very excellent, and the effect of suppressing the loss of alveolar bone caused by inflammation is also very excellent.
실시예 4. 동물모델을 활용한 CBD와 Taurine 병용투여의 치주염 억제 효능 분석Example 4. Analysis of periodontitis inhibition efficacy of combined administration of CBD and Taurine using animal model
[실험 방법] [Experimental Method]
시험에 공시된 rat의 준비Preparation of rats published for testing
Rat의 구매는 Nara Biotech Pyeongtaek Plant (Gyeonggi-do, Korea)에서 구매하였으며, 시험에 공시된 rat은 6주령 Sprague-Dawley계 수컷 rat(M/6W, 180-200g)을 사용하여 시험에 공시하였다. 동물실험은 전북대학교 Institutional Animal Care and Use Committee(IACUC guidelines)의 규정에 따라 행하였다. Rats were purchased from Nara Biotech Pyeongtaek Plant (Gyeonggi-do, Korea), and the rats used in the test were 6-week-old Sprague-Dawley male rats (M/6W, 180-200g). Animal experiments were conducted in accordance with the regulations of the Chonbuk National University Institutional Animal Care and Use Committee (IACUC guidelines).
안정화 기간stabilization period
안정화 기간 동안 시험에 공시된 rat은 20-24℃, 습도는 50-60%로 유지하면서 낮과 밤의 주기는 각각 12시간으로 조절한 동물 사육실에서 1주일간 자유 사료 및 음수섭취를 통해 실험환경에 적응시켰다. During the stabilization period, the rats tested were exposed to the experimental environment by consuming free food and drinking water for one week in an animal breeding room maintained at 20-24°C and humidity at 50-60%, with the day and night cycles adjusted to 12 hours each. adapted.
치주염 유발Causes periodontitis
1) 치주염 유발균 (P. gingivalis)의 준비1) Preparation of periodontitis-causing bacteria (P. gingivalis)
치주염균(P. gingivalis)은 한국구강미생물자원은행에서 분양받아 사용하였다(PG 2797). 치주염 유발균의 준비는 실험 시작일 3주일 전에 혐기성 상태의 밴치에서 배양배지 내에 접종 후 3주일간 배양을 실시하였다. 3주일간 배양된 치주염균은 육안으로 배양액의 탁도와 배양접시에 접종한 균의 성장 정도를 이용해 7일간 치주염 유발시에 각각 사용되었다. Periodontitis bacteria (P. gingivalis) was purchased from the Korea Oral Microbial Resources Bank (PG 2797). Periodontitis-causing bacteria were prepared by inoculating the culture medium in an anaerobic bench 3 weeks before the start of the experiment and culturing for 3 weeks. Periodontitis bacteria cultured for 3 weeks were used to induce periodontitis for 7 days, using the turbidity of the culture medium visually and the growth rate of the bacteria inoculated in the culture dish.
2) 치주염 유발 (Periodontitis)2) Causes periodontitis (Periodontitis)
치주염균이 처리된 밴드(TP Orthodontics, Inc., Seoul, Korea)를 이용하여 묶음(ligature)으로 치주염을 유발시킨다. 결착밴드(band suture)는 치주염균이 있는 현탁액(slurry)에 보관하여 치주염균이 결착밴드에 잘 혼합된 상태에서 결착밴드를 처리할 수 있도록 하였다. 결착밴드는 적절한 크기로 절제 후 상악 어금니(premolar of mandibular quadrant) 앞쪽 부위에 ligature 처리하여 치주염을 유발하였으며, 3일 후 결착밴드의 손실을 확인하여 손실된 부위에 재차 결착밴드를 삽입하여 7일간 치주염을 유발하였다. Periodontitis is induced by ligature using a band treated with periodontitis bacteria (TP Orthodontics, Inc., Seoul, Korea). The band suture was stored in a slurry containing periodontitis bacteria so that the band suture could be processed while the periodontitis bacteria were well mixed into the band. The bonding band was excised to an appropriate size and then ligatured to the area in front of the maxillary molars (premolar of mandibular quadrant) to induce periodontitis. After 3 days, loss of the bonding band was confirmed, and the bonding band was inserted again into the lost area to treat periodontitis for 7 days. caused.
투약dosage
1) 투약방법1) Dosage method
치주염 유발 7일 후 치주염이 유발되었는지 Pocket depth를 이용하여 측정 후 2주 동안 매일 조제물을 경구 투여하였다. 투여 시 간섭현상 (위 내 존대 투여 시 입안에 조제물이 묻는 것 및 각 조제물의 주사기 내 잔존)을 막기 위해 존대 투여 시 휴지로 존대에 묻어 있는 물질을 제거 후 투약을 실시하였으며, 주사기 내 잔존물질을 제거하기 위해 투여 전 물에서 3∼5회 세척 후 투여하였다.Seven days after the induction of periodontitis, the occurrence of periodontitis was measured using pocket depth, and then the preparation was administered orally every day for two weeks. To prevent interference during administration (during intragastric administration, the preparation gets on the mouth and residues of each preparation in the syringe), when administering the supplement, substances on the preparation were removed with a tissue before administration, and any remaining substances in the syringe were administered. To remove , it was administered after washing 3 to 5 times in water before administration.
실험에 공시된 총 마리 수는 50마리로, 각 처리구별 10마리씩 총 5처리구 50마리를 실험에 공시하였으며, 50마리 중 각 처리구 당 10마리씩 사용하였다. Control은 healthy한 그룹으로 치주염 유발을 하지 않은 상태의 그룹이며, vehicle은 치주염 유발 후 투약을 하지 않고 물만을 투약한 대조구다. 또한 Insadol(4.5 mg/kg Dongkook Pharmaceutical, Korea)은 투약 대조구로서 시중에 판매되는 Insadol을 구매하여 사용하였으며 물에 녹여 투여하였다. Low dose CBD+Taurine(L-CBD+Taurine), High dose CBD+Taurine(H-CBD+Taurine) 처리구는 CBD의 농도에 따른 치주염 효능을 검토하기 위해 Taurine(100mg/kg Sigma-Aldrich, Seoul, Korea)을 물에 녹여 고정 농도로 각각 투여하고 CBD는 물에 녹지 않아 Corn oil(Sigma-Aldrich)에 녹여 L-CBD(2 mg/kg), H-CBD(20mg/kg)의 농도로 각각 투여하였다.The total number of animals presented in the experiment was 50, and a total of 50 animals in 5 treatments, 10 animals in each treatment group, were used in the experiment. Among the 50 animals, 10 animals were used in each treatment group. Control is a healthy group in which periodontitis was not induced, and vehicle is a control group in which only water was administered without medication after periodontitis was induced. In addition, Insadol (4.5 mg/kg Dongkook Pharmaceutical, Korea) was purchased commercially as a control and was administered by dissolving it in water. Low dose CBD + Taurine (L-CBD + Taurine) and high dose CBD + Taurine (H-CBD + Taurine) treatments were treated with Taurine (100mg/kg Sigma-Aldrich, Seoul, Korea) to examine the efficacy of periodontitis according to CBD concentration. ) was dissolved in water and administered at a fixed concentration, and CBD was not soluble in water, so it was dissolved in corn oil (Sigma-Aldrich) and administered at a concentration of L-CBD (2 mg/kg) and H-CBD (20mg/kg). .
Pocket depth 측정Pocket depth measurement
Pocket depth의 측정은 치주낭 깊이를 Pocket depth probe를 이용하여 측정하였다. 치주염 유발 후 조제물의 투약 시 치주염 억제 효과를 pocket depth의 길이를 이용하여 측정하였다. 측정 시기는 치주염 유발 후 7일차, 14일차, 21일차 총 3회 측정하여 치주염 억제 효능을 검토하였다. Pocket depth was measured using a pocket depth probe. The effect of suppressing periodontitis upon administration of the preparation after inducing periodontitis was measured using the length of pocket depth. The measurement period was measured three times on the 7th, 14th, and 21st days after the induction of periodontitis to examine the efficacy of suppressing periodontitis.
Alveolar Bone Loss 측정을 위한 Micro-CT 분석Micro-CT analysis for measuring alveolar bone loss
전북대학교 공동실험실습실에 있는 High resolution in vivo X-ray microtomograph(HR Micro-CT)(Bruker MicroCT, Kontich, MA, USA)를 이용하여 Aleveolar bone loss를 측정하였다. 총 치주염 유발 후 20일차까지 조제물을 투여 후 21일 Sacrificed를 진행하여 오른쪽 상악골 (Right maxillary)을 샘플채취하여 micro-CT를 측정하였다. 각 처리구는 two-dimensional measurement software(Bruker dataviewer, USA)를 이용하여 bone mineral density (BMD)를 측정였다. Aleveolar bone loss was measured using high resolution in vivo After inducing total periodontitis, the preparation was administered until the 20th day, and then Sacrificed on the 21st day, the right maxillary bone was sampled and micro-CT was measured. Bone mineral density (BMD) of each treatment group was measured using two-dimensional measurement software (Bruker dataviewer, USA).
[실험 결과][Experiment result]
CBD와 Taurine 병용투여 시 치주염에 의한 Pocket depth 억제 효능 분석Analysis of efficacy in suppressing pocket depth caused by periodontitis when CBD and Taurine are administered together
CBD와 Taurine의 병용투여 시 농도에 따른 치주염 억제 효능을 검토하기 위해 pocket depth를 측정하고 그 결과를 도 5에 나타내었다. 측정 결과, 치주염 유발 7일 후 14일까지 7일 동안, H-CBD+Taurine 그룹에서 pocket depth의 억제가 가장 높게 나타났으며, 21일차 pocket depth에서도 H-CBD+Taurine 그룹에서 pocket depth의 억제가 가장 높게 나타났다 (***, P〈0.001). CBD를 높은 농도로 처리 시 가장 높은 치주염 억제 효능을 나타냈으며, 특히 Insadol보다 더 높은 치주염 억제 효능을 나타내는 것으로 확인되었다. To examine the efficacy of suppressing periodontitis according to concentration when coadministering CBD and Taurine, pocket depth was measured and the results are shown in Figure 5. As a result of the measurement, the highest inhibition of pocket depth was observed in the H-CBD+Taurine group for 7 days from the 7th day to the 14th day of periodontitis induction, and even on the 21st day, the inhibition of pocket depth was observed in the H-CBD+Taurine group. It appeared highest (***, P<0.001). When CBD was treated at a high concentration, it showed the highest efficacy in suppressing periodontitis. In particular, it was confirmed to have a higher efficacy in suppressing periodontitis than Insadol.
CBD와 Taurine 병용투여 시 치주염에 의한 치조골 소실(alveola bone loss) 억제 효능 분석Analysis of efficacy in suppressing alveola bone loss caused by periodontitis when CBD and Taurine are administered together
CBD와 Taurine의 병용투여 시 농도에 따른 Alveolar bone loss 억제 효능을 검토하기 위해 BMD를 측정하고 그 결과를 도 6에 나타내었다. 측정 결과, H-CBD+Taurine 그룹에서 치주염에 의한 BMD의 감소 억제가 가장 높게 나타났는바, 높은 농도의 CBD를 taurine과 병용처리 시 매우 우수한 치주염 치료 효능이 있음을 알 수 있다 (*, P〈0.05; **, P〈0.01; ***, P〈0.001). To examine the efficacy of suppressing alveolar bone loss according to concentration when coadministering CBD and Taurine, BMD was measured and the results are shown in Figure 6. As a result of the measurement, the H-CBD + Taurine group showed the highest inhibition of BMD reduction due to periodontitis. It can be seen that high concentration of CBD in combination with taurine has excellent periodontitis treatment efficacy (*, P < 0.05; **, P < 0.01; ***, P < 0.001).
이하, 본 발명에 따른 상기 CBD 및 타우린을 유효성분으로 함유하는 의약품 또는 식품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다. 상기 유효성분을 이용하여 하기와 같은 조성성분 및 조성비에 따라 제조예 1 또는 2의 의약품 또는 식품 조성물을 통상적인 방법에 따라서 제조하였다.Hereinafter, an example of manufacturing a medicine or food containing the CBD and taurine as active ingredients according to the present invention will be described, but the present invention is not intended to be limited, but merely explained in detail. Using the above active ingredients, the pharmaceutical or food composition of Preparation Example 1 or 2 was prepared according to a conventional method according to the composition ingredients and composition ratios as follows.
[제조예 1] 약학적 조성물의 제조[Preparation Example 1] Preparation of pharmaceutical composition
<1-1> 산제의 제조<1-1> Production of powder
CBD 및 타우린 20 ㎎CBD and taurine 20mg
유당수화물 100 ㎎ Lactose hydrate 100 mg
탈크 10 ㎎Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled into an airtight bubble to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of tablets
CBD 및 타우린 10 ㎎CBD and taurine 10mg
옥수수전분 100 ㎎ Corn starch 100 mg
유당수화물 100 ㎎ Lactose hydrate 100 mg
스테아르산마그네슘 2 ㎎ Magnesium stearate 2 mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above ingredients, tablets were manufactured by tableting according to a conventional tablet manufacturing method.
<1-3> 캅셀제의 제조<1-3> Production of capsules
CBD 및 타우린 10 ㎎CBD and taurine 10mg
미결정셀룰로오스 3 ㎎ Microcrystalline cellulose 3 mg
유당수화물 14.8 ㎎Lactose hydrate 14.8 mg
스테아르산마그네슘 0.2 ㎎Magnesium stearate 0.2 mg
상기의 성분을 혼합한 후, 통상의 캅셀제의 제조방법에 따라서 젤라틴캡슐에 충전하여 캅셀제를 제조하였다.After mixing the above ingredients, a capsule was prepared by filling a gelatin capsule according to a typical capsule preparation method.
<1-4> 주사제의 제조<1-4> Preparation of injections
CBD 및 타우린 10 ㎎CBD and taurine 10mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎Sterile distilled water for injection 2974 mg
인산일수소나트륨 26 ㎎Sodium monohydrogen phosphate 26 mg
상기의 성분을 혼합한 후, 통상의 주사제의 제조방법에 따라 1앰플당(2mL) 상기의 성분 함량으로 제조하였다.After mixing the above ingredients, it was prepared with the above ingredient content per 1 ampoule (2 mL) according to a typical injection preparation method.
<1-5> 액제의 제조<1-5> Preparation of liquid
CBD 및 타우린 10 ㎎CBD and taurine 10mg
이성화당 10 ㎎10 mg of isomerized sugar
만니톨 5 ㎎Mannitol 5mg
정제수 적량Proper amount of purified water
레몬향 적량Lemon flavor appropriate amount
상기의 성분을 통상의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 정제수를 가하여 전체 100mL로 조절한 후 멸균시켜 갈색병에 충진하여 액제를 제조한다. The above ingredients are dissolved in purified water according to the usual manufacturing method, an appropriate amount of lemon flavor is added, then purified water is added to adjust the total to 100 mL, then sterilized and filled into a brown bottle to prepare a liquid.
[제조예 2] 건강기능식품의 제조[Manufacture Example 2] Manufacture of health functional food
<2-1> 건강보조식품의 제조<2-1> Manufacturing of health supplements
CBD 및 타우린 10 ㎎CBD and taurine 10mg
비타민 혼합물 적량Vitamin mixture dosage
비타민 A 아세테이드 70 ㎍Vitamin A acetate 70 μg
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B 1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B 2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B 6 0.5 mg
비타민 B12 0.2 ㎍Vitamin B 12 0.2 ㎍
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 ㎎Nicotinamide 1.7 mg
엽산 50 ㎍Folic acid 50 μg
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture appropriate amount
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Monobasic Potassium Phosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 30 ㎎Potassium citrate 30 mg
탄산칼슘 100 ㎎ Calcium carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.The composition ratio of the above vitamin and mineral mixture is a mixture of components relatively suitable for health food in a preferred embodiment, but the mixing ratio may be modified arbitrarily. The above ingredients are mixed according to a typical health food manufacturing method, and then , granules can be manufactured and used to manufacture health food compositions according to conventional methods.
<2-2> 건강음료의 제조<2-2> Manufacturing of health drinks
CBD 및 타우린 10 mg10 mg CBD and taurine
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 gVitamin E (powder) 100 g
젖산철 19.75 g19.75 g iron lactate
산화아연 3.5 g3.5 g zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 gVitamin A 0.2 g
비타민 B1 0.25 gVitamin B1 0.25 g
비타민 B2 0.3 gVitamin B2 0.3 g
정제수 정량Purified water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above ingredients according to a typical health drink manufacturing method, stirring and heating at 85° C. for about 1 hour, the resulting solution was filtered, obtained in a sterilized 2-liter container, sealed, sterilized, and refrigerated, followed by the present invention. It is used in the production of health drink compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The composition ratio is a preferred embodiment of mixing ingredients that are relatively suitable for beverages of preference, but the mixing ratio may be arbitrarily modified depending on regional or ethnic preferences such as demand class, country of demand, and intended use.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

Claims (8)

  1. 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  2. 청구항 1에 있어서, In claim 1,
    상기 칸나비디올은 하기 화학식 1로 표시되는 것을 특징으로 하는 치주염 예방 또는 치료용 약학적 조성물.The cannabidiol is a pharmaceutical composition for preventing or treating periodontitis, characterized in that it is represented by the following formula (1).
    [화학식 1][Formula 1]
    Figure PCTKR2023011476-appb-img-000005
    Figure PCTKR2023011476-appb-img-000005
  3. 청구항 1에 있어서, In claim 1,
    상기 타우린은 하기 화학식 2로 표시되는 것을 특징으로 하는 치주염 예방 또는 치료용 약학적 조성물.The taurine is a pharmaceutical composition for preventing or treating periodontitis, characterized in that it is represented by the following formula (2).
    [화학식 2][Formula 2]
    Figure PCTKR2023011476-appb-img-000006
    Figure PCTKR2023011476-appb-img-000006
  4. 청구항 1에 있어서,In claim 1,
    상기 유효성분은 TNF-α 및 IL-1β를 억제하는 것을 특징으로 치주염 예방 또는 치료용 약학적 조성물.The active ingredient is a pharmaceutical composition for preventing or treating periodontitis, characterized in that it inhibits TNF-α and IL-1β.
  5. 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 의약외품 조성물.A quasi-drug composition for preventing or improving periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  6. 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 치주염 예방 또는 개선용 식품 조성물.A food composition for preventing or improving periodontitis comprising cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
  7. 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 조성물을 개체에 투여 또는 복용시키는 단계를 포함하는 치주염 예방 또는 치료방법.A method for preventing or treating periodontitis, comprising administering or taking a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients to an individual.
  8. 칸나비디올 및 타우린, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 포함하는 조성물의 치주염 예방 또는 치료용도.Use for preventing or treating periodontitis of a composition containing cannabidiol and taurine, or a pharmaceutically acceptable salt thereof, as active ingredients.
PCT/KR2023/011476 2022-10-24 2023-08-04 Composition comprising cannabidiol and taurine for preventing or treating periodontitis WO2024090747A1 (en)

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